We study the expression of MHC gene products on metaatatic as distinct from nonmetastatic clones, and their function in controlling the metastatic phenotype. Thus, analyzing a large number of clones of the metastatic 3LL Lewis lung carcinoma (of H-2[unreadable]b[unreadable] origin), we found that the lower the H-2K[unreadable]b[unreadable]/H-2D[unreadable]b[unreadable] ratio on tumor cell surface, the higher their metastatic competence. Interferon alpha and beta and retinoic acid, applied in vitro, caused a net increase in the cell surface expression of H-2D[unreadable]b[unreadable] glycoproteins. This was associated with a significant increase of the metastatic properties. Gamma-interferon, on the other hand, caused a relative increase in H-2K[unreadable]b[unreadable] expression, resulting in a significant decrease of metastatic competence. Functional studies indicated that clones of high H-2K/H-2D ratio (nonmetastatic) are significantly more immunogenic and more susceptible to immune responses than clones of low H-2K/H-2D ratio (metastatic). T-cell mediated immune responses participate significantly in controlling the expression of the metastatic phenotype. Gene cloning of the MHC of the tumor cells is carried out to investigate the molecular basis of suppression in H-2K expression in metastatic clones. A similar approach is applied to a metastatic model of a heterozygous (H-2[unreadable]b[unreadable] x H-2[unreadable]k[unreadable])F[unreadable]1[unreadable] origin, the T10 sarcoma. Both metastatic and nonmetastatic clones do not express the H-2K of either haplotype. Immunoselection experiments indicated that the metastatic phenotype is determined just by the expression of the H-2D[unreadable]k[unreadable]. Nonmetastatic clones, which differ from the metastatic only in H-2 expression, are significantly more immunogenic. Transfection of a metastatic clone with H-2K[unreadable]b[unreadable] or H-2K[unreadable]k[unreadable] genes, followed by the cell surface expression of these genes, resulted in the abrogation of the metastatic competence. This was correlated with a significant increase in the immunogenic properties of the transfected cells. The molecular basis of the differential structure, expression, and function of class 1 antigens on metastatic tumors is investigated. This is carried out in parallel with studies on oncogenes in metastatic and nonmetastatic clones. (IB)